1. Field of the Invention
The invention relates to protection against Anthrax-mediated biotoxicity.
2. Summary of the Related Art
Bacillus anthracis is one of the most dangerous potential biological weapons. Currently, there is no effective treatment for inhalational anthrax, beyond the administration of antibiotics shortly after exposure. Time delay reduces the effectiveness of antibiotic treatment. Dixon et al., Anthrax. N. Engl. J. Med.: 341, 815-826 (1999) teaches that major factors playing a role in anthrax infection are the cytotoxic effect of anthrax toxin, and bacteremia leading to oxygen and nutritional substance deprivation, accumulation of various bacterial and host toxic products with eventual organ failure and death.
Brossier et al., Toxicon. 39: 1747-1755 (2001) teaches that the two anthrax toxins are formed by three different proteins: protective antigen (PA) which either combines with lethal factor (LF) to form lethal toxin (LeTx), or with edema factor (EF) to form edema toxin (EdTx). LF and EF are enzymes targeting substrates within the cytosol, and PA facilitates their transport across the cell membrane forming a heptameric pore. PA assembles into a ring-shaped heptamer with a negatively charged lumen and exposes a hydrophobic surface for binding of LF and EF. Petosa et al., Nature 385: 833-838 (1997) teaches the three-dimensional structure of the PA pore.
Karginov et al., FEMS Immun. Med. Microb. 40: 71-74 (2004) teaches that treatment of Bacillus anthracis infected mice with a combination of the antibiotic ciprofloxacin and partially purified antibodies against anthrax protective antigen dramatically increased survival rates in comparison with antibiotic treatment alone.
Although promising, antibodies are less attractive as potential drugs in comparison with low molecular weight compounds, which offer potentially better penetration through membranes and are not sensitive to proteases.
Therefore, there is a need for new safe and efficient treatments to supplement to traditional antibiotic intervention.